Concisely, the specific aims and methodology of this research proposal are the following: I) To define the requirements (hormonal) for maximum growth of normal human breast tissues maintained in the athymic nude mouse. a) Slices of normal human breast tissues will be transplanted s.c. to and maintained (1-9 months) in hormone treated athymnic nude mice. b) Growth of the epitehlium in the human breast tissue grafts will be asessed by: 1) autoradiographic analysis of 3H-thymidine incorporation into DNA (labelling index) and 2) whole-mount morphological analysis. II) To define the requirements (hormonal) for macimum differentiation (lactation) of normal human breast tissues maintained in the athymic nude mouse. a) Slices of normal human breast tissues will be transplanted s.c. to and maintained (1-9 months) in hormone treated athymic nude mice. b) Secretion (lactation) of the human breast tissue grafts will be assessed by: 1) Alpha-lactalblmin radioimmunoassay and 2) histological analysis. In the proposed reasearch, we will strive to demonstrate that normal human breast tissues, when transplanted to hormone-treated athymic nude mouse, can function precisely, as it does in the human being, i.e., to grow and lactate. If this can be demonstrated, we will then have for the first time, an ex vivo in vivo model to study development, growth, differentiation and ultimately tumorigenesis of the human breast.